Reduction of tooth staining derived from cationic antibacterials

ABSTRACT

Examples of cationic antimicrobial agent include quaternary ammonium compounds such as cetylpyridinium chloride, cetyl pyridinium fluoride, tetradecylpyridinium chloride, N-tetradecyl-4-ethyl pyridinium chloride and domiphen bromide; chlorhexidine; and metal ion sources to supply metal ions such as stannous, zinc or copper.

TECHNICAL FIELD

The present invention relates to oral care compositions containing anagent to eliminate or reduce tooth staining, specifically stainingderived from cationic antimicrobial agents used in oral carecompositions to reduce oral bacteria and to prevent and treatbacteria-mediated diseases or conditions of the oral cavity includingdental plaque, caries, calculus, gingivitis, periodontal disease andbreath malodor.

BACKGROUND OF THE INVENTION

Cationic materials which possess antimicrobial activity have been usedin oral compositions to counter oral bacteria and to prevent and treatconditions caused by bacteria in the oral cavity, such as formation ofdental plaque and calculus. The formation of dental plaque and calculusand failure to stop their proliferation are the primary cause of dentalcaries, gingivitis, periodontal disease, and tooth loss. Dental plaqueis a mixed matrix of bacteria, epithelial cells, leukocytes, macrophagesand other oral exudate. Bacteria comprise approximately three-quartersof the plaque matrix. Any given sample of dental plaque could contain asmany as 400 different varieties of microorganisms. This mix includesboth aerobic and anaerobic bacteria, fungi, viruses and protozoa. Thismatrix of organisms and oral exudate continues to expand and coalesceswith other plaque growths situated nearby. The bacteria synthesizelevans and glucans from sucrose found in the oral cavity providingenergy for the microorganisms. These glucans, levans, and microorganismsform an adhesive skeleton for the continued proliferation of plaque.Dental calculus, or tartar as it is sometimes called, is a deposit whichforms on the surfaces of the teeth at the gingival margin. Maturecalculus consists of an inorganic portion which is largely calciumphosphate arranged in a hydroxyapatite crystal lattice structure similarto bone, enamel and dentine. An organic portion is also present andconsists of desquamated epithelial cells, leukocytes, salivary sediment,food debris and various types of microorganisms. Developing plaque canadhere most easily at relatively irregular surfaces, such as thoseafforded by calculus. Calculus and plaque along with behavioral andenvironmental factors lead to formation of dental stains, significantlyaffecting the aesthetic appearance of teeth. Behavioral andenvironmental factors that contribute to teeth staining propensityinclude regular use of products that contain staining chemicals or colorbodies such as coffee, tea, cola or tobacco and use of stain promotingoral products, such as those containing cationic antimicrobial agents.

Among the most common of cationic antimicrobial agents known to causetooth staining are quaternary ammonium compounds such as cetylpyridiniumchloride and metal ion sources such as stannous fluoride and stannouschloride. The tooth staining potential of these cationic materials haslong been documented. Among the many approaches that have been suggestedto reduce and control tooth staining and to whiten teeth is by the useof bleaches or oxidants such as peroxide. Essentially, bleaches act byoxidizing color bodies and existing stains. However, bleaches added tooral care products are typically present in low concentrations due tostability and safety limits. At these low concentrations, bleaches suchas peroxide, are generally ineffective to control stain and whitenteeth. Furthermore, bleaches do not functionally act to preventacquisition of stains.

There continues to be a need for oral care products that provideenhanced overall cleaning and hygiene while also controlling toothstaining. Chemical technologies have now been identified that caneffectively reduce tooth staining derived from cationic antimicrobialssuch as CPC. These chemical agents do not involve the use of bleaches oroxidants and significantly do not compromise the bioavailability of thecationic antimicrobials and therefore, their antimicrobial potency.

SUMMARY OF THE INVENTION

The present invention is directed to oral care compositions comprisingin a pharmaceutically acceptable carrier, a combination of a cationicantimicrobial agent that causes tooth staining and an anti-stain agentcomprising at least two different materials from the following chemicalgroups:

Group 1. anionic agents,

Group 2. aldehydes, ketones, and other reactive carbonyl compounds and

Group 3. nonionic ethoxylated surfactants.

Examples of Group 1 anionic agents are compounds and polymers containingphosphate, carboxy or sulfate groups such as carboxymethyl dextran(degree of substitution=0.1, MW=10,000) and tetrapotasium pyrophosphate.

Examples of Group 2 aldehydes, ketones and other reactive carbonylcompounds are 4-methoxybenzaldehyde (anisaldehyde);1,3-benzodioxole-5-carbaldehyde (heliotropin); 3,4-Dimethoxybenzaldehyde(veratraldehyde); 3-methyl-1,2-cyclopentadione; phenethyl formate,acetophenone; phenylacetaldehyde; 4-methylacetophenone;ρ-toluacetaldehyde; 3,5,5-trimethyl-2-cyclohexene-1-one (isophorone);gamma-undecalactone; or ρ-methylcinnamaldehyde.

Examples of Group 3 nonionic ethoxylated surfactants are ethoxylatedlinear alcohols such as those wherein the number of carbons in thealcohol chain is between about 18 to 55, the ethoxy units by weight isat least 80% and the average molecular weight of the polymer is about2000 to about 5000.

Examples of cationic antimicrobial agent include quaternary ammoniumcompounds such as cetylpyridinium chloride, tetradecylpyridiniumchloride, N-tetradecyl-4-ethyl pyridinium chloride and domiphen bromide;metal ion sources to supply metal ions such as stannous, zinc andcopper; and chlorhexidine.

These and other features, aspects, and advantages of the presentinvention will become evident to those skilled in the art from thedetailed description which follows.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 illustrates the reaction between an aldehyde and a salivaryprotein by thioacetal formation.

FIG. 2 is a summary of the protocols used in the HAP-Pellicle and BovineTooth in vitro staining models.

DETAILED DESCRIPTION OF THE INVENTION

While the specification concludes with claims particularly pointing outand distinctly claiming the invention, it is believed that the presentinvention will be better understood from the following description.

All percentages and ratios used hereinafter are by weight of totalcomposition, unless otherwise indicated. All percentages, ratios, andlevels of ingredients referred to herein are based on the actual amountof the ingredient, and do not include solvents, fillers, or othermaterials with which the ingredient may be combined as a commerciallyavailable product, unless otherwise indicated. All measurements referredto herein are made at about 25° C. unless otherwise specified.

Herein, “comprising” means that other steps and other components whichdo not affect the end result can be added. This term encompasses theterms “consisting of” and “consisting essentially of.”

As used herein, the word “include,” and its variants, are intended to benon-limiting, such that recitation of items in a list is not to theexclusion of other like items that may also be useful in the materials,compositions, devices, and methods of this invention.

As used herein, the words “preferred”, “preferably” and variants referto embodiments of the invention that afford certain benefits, undercertain circumstances. However, other embodiments may also be preferred,under the same or other circumstances. Furthermore, the recitation ofone or more preferred embodiments does not imply that other embodimentsare not useful, and is not intended to exclude other embodiments fromthe scope of the invention.

By “oral care composition” is meant a product, which in the ordinarycourse of usage, is not intentionally swallowed for purposes of systemicadministration of particular therapeutic agents, but is rather retainedin the oral cavity for a time sufficient to contact substantially all ofthe dental surfaces and/or oral tissues for purposes of oral activity.The oral care composition may be in various forms including toothpaste,dentifrice, tooth gel, subgingival gel, mouth rinse, mousse, foam,denture product, mouthspray, lozenge, chewable tablet or chewing gum.The oral care composition may also be incorporated onto strips or filmsfor direct application or attachment to oral surfaces.

The term “dentifrice”, as used herein, means paste, gel, or liquidformulations unless otherwise specified. The dentifrice composition maybe a single phase composition or may be a combination of two or moreseparate dentifrice compositions. The dentifrice composition may be inany desired form, such as deep striped, surface striped, multilayered,having the gel surrounding the paste, or any combination thereof. Eachdentifrice composition in a dentifrice comprising two or more separatedentifrice compositions may be contained in a physically separatedcompartment of a dispenser and dispensed side-by-side.

The term “dispenser”, as used herein, means any pump, tube, or containersuitable for dispensing compositions such as dentifrices.

The term “mouth rinse”, as used herein, includes liquid formulationsreferred in the art as mouthwashes or dental rinses, mouth sprays,dental solutions and irrigation fluids.

The term “teeth” refers to natural teeth as well as artificial teeth ordental prosthesis.

The terms “pharmaceutically acceptable carrier”, “orally acceptablecarrier” or “excipients” include safe and effective materials andconventional additives such as those used in oral care compositionsincluding but not limited to fluoride ion sources, antimicrobial agents,anti-inflammatory agents, anti-calculus or anti-tartar agents,desensitizing agents, peroxide sources, abrasives such as silica,buffering agents, alkali metal bicarbonate salts, thickening materials,humectants, water, surfactants, emulsifying agents, anti-stain agents,tooth substantive agents, titanium dioxide, xylitol, essential oils, acoolant, a sweetening agents or other sensates and coloring agents.

The term “essential oils” as used herein refers to volatile oilsdistilled or expressed from plants and constituents of these volatileoils. Typical essential oils and their main constituents are thoseobtained for example from thyme (thymol, carvacrol), oregano (carvacrol,terpenes), lemon (limonene, terpinene, phellandrene, pinene, citral),lemongrass (citral, methylheptenone, citronellal, geraniol), orangeflower (linalool, β-pinene, limonene), orange (limonene, citral), anise(anethole, safrol), clove (eugenol, eugenyl acetate, caryophyllene),rose (geraniol, citronellol), rosemary (borneol, bornyl esters,camphor), geranium (geraniol, citronellol, linalool), lavender (linalylacetate, linalool), citronella (geraniol, citronellol, citronellal,camphene), eucalyptus (eucalyptol); peppermint (menthol, menthylesters), spearmint (carvone, limonene, pinene); wintergreen (methylsalicylate), camphor (safrole, acetaldehyde, camphor), bay (eugenol,myrcene, chavicol), cinnamon (cinnamaldehyde, cinnamyl acetate,eugenol), tea tree (terpinen-4-ol, cineole), and cedar leaf (α-thujone,β-thujone, fenchone). Essential oils are widely used in perfumery and asflavorings, medicine and solvents [See Kirk-Othmer Encyclopedia ofChemical Technology, 4^(th) Edition and The Merck Index, 13^(th)Edition].

Active and other ingredients useful herein may be categorized ordescribed by their cosmetic and/or therapeutic benefit or theirpostulated mode of action or function. However, the active and otheringredients useful herein can, in some instances, provide more than onecosmetic and/or therapeutic benefit or function or operate via more thanone mode of action. Therefore, classifications herein are made for thesake of convenience and are not intended to limit an ingredient to theparticularly stated application or applications listed.

In one embodiment of the present invention, oral care compositions areprovided comprising a cationic antimicrobial agent comprising one or amixture of a quaternary ammonium compound selected from cetylpyridiniumchloride, tetradecylpyridinium chloride, N-tetradecyl-4-ethyl pyridiniumchloride or domiphen bromide; a stannous ion source; a zinc ion sourceor a copper ion source in combination with an anti-staining agent. Theanti-staining agent will preferably comprise one or more materials fromeach of at least two of the following chemical groups:

Group 1. anionic agents,

Group 2. aldehydes, ketones and reactive carbonyl compounds and

Group 3. nonionic ethoxylated surfactants.

The cationic antimicrobial agents effectively promote oral hygiene,particularly by controlling plaque and calculus proliferation. However,their use has been observed to lead to staining of tooth surfaces ordiscoloration. The exact mechanisms for the formation of dental stainderived from the use of these cationic antimicrobials have not beenclearly established. One explanation that has been offered is that asthe cationic antimicrobial agents remove plaque they also denatureprotein from saliva in the oral environment and the denatured proteincan then act as a nucleating agent which is deposited onto and stains ordiscolors teeth. Another theory is that in the absence of dental plaque,additional Ca⁺² and PO4⁻³, particularly from saliva, can be deposited onthe tooth surface and such deposits can include color bodies whichultimately stain the tooth surface as a calcified deposit thereon.

Studies were conducted at the Procter & Gamble laboratories to furtherelucidate the staining problem. Using cetyl pyridinium chloride (CPC) asthe stain promoting antimicrobial, it was observed that initial stainformation with CPC occurs on the pellicle surface of the teeth. Thisstain is a result of the interaction between salivary proteins such asmucin and dietary chromogens or color bodies such as tea polyphenols.The observed stain is exacerbated in the presence of CPC or othercationic antimicrobials such as stannous salts. As has been reported inliterature, there are significant interactions between the basic prolinerich proteins in saliva and tea polyphenols [See e.g., J. Dent. Res.,84(1), 73-781 (2005); Biochem. J., 297, 249-260 (1994); “Grape and WineTannins Precipitation by Proline Rich Proteins”, Poster at the 2^(nd)International Electronic Conference of Synthetic Organic Chemistry(ECSOC-2, Sep. 1-30, 1998)]. In fact it has been reported that sodiumdodecylsulfate (SDS) polyacrylamide gel electrophoresis of a mixture ofsaliva and tea extract resulted in the disappearance of the basicproline rich protein bands indicating a precipitation of the basicproline rich proteins with tea polyphenols. The proline rich proteinsare inducible in the stomach and saliva and is the body's naturaldefense mechanism to complex the larger polyphenols to precipitate them,preventing their absorption and hence reducing their toxicity. Theinteraction of sodium dodecylsulfate (SDS) and nonionic surfactants withmucin has also been reported [Langmuir, 18, 9383-9392 (2002)]. Ourstudies have demonstrated that there is a similar interaction betweenCPC with other anionic proteins in saliva resulting in the precipitationof the protein and CPC on the tooth surface. The co-precipitate of CPCand protein subsequently interacts with dietary chromogens such as teapolyphenols resulting in tooth staining.

We have found that by the use of certain anionic agents, we are able toreduce aggregation of salivary proteins, either by direct hydrophobic(insertion into non polar region of the protein) or charged interactionof the anionic agent with the salivary proteins or by the formation of acounter ion with the pyridinium ring of the CPC. The anionic agent ismore tightly bound to the pyridinium ring than the chloride ion, whichthen reduces the interaction of CPC with the salivary proteins.

Some aldehydes have been also been demonstrated to react with salivaryproteins by thioacetal formation as illustrated in FIG. 1, therebyreducing the negative charge density on the surface of the protein andthus, the protein interaction with the positively charged pyridiniumring of CPC.

When combined, the anionic agent and aldehyde provide even betteranti-staining results compared to using these agents separately. It isbelieved the combination enables stronger interaction between thealdehyde and the protein compared to the interaction between the proteinand CPC, as CPC is now tightly bound to a large anionic counter ion andthus less available to interact with the protein. This would explain theobserved synergy when using the combination of a lightly charged anionicagent and certain aldehydes or ketones in studies described below.

Similarly we have demonstrated that the use of ethoxylates having theright balance of alkyl and ethoxy units can effectively solubilizesalivary proteins, thereby reducing staining. Importantly, the use ofthe above agents do not significantly impact the bioavailability of CPC,which is surprising and unexpected, given previous findings that thebioavailability of quaternary ammonium antimicrobials is affected by thepresence of anionic materials and even nonionic materials that have somepartial negative charge (due to hydroxyl, ester, aldehydes and ketonefunctional groups) as in some ethoxylated surfactants (US20050169852A1to Roberge, et al.).

A similar approach can be used to control tooth staining derived fromother cationic antimicrobials such as stannous, zinc or copper saltsused in dentifrice, gel or rinse oral care products.

Evaluation of Tooth Staining Potential of Cationic Antimicrobials andAnti-Staining Activity of Agents:

A. In Vitro Models

Two models were used to evaluate tooth staining potential ofcompositions containing cationic antimicrobials. CPC was used as themodel stain-promoting antimicrobial. The general protocols for themodels described below are summarized in FIG. 2.

HAP-Pellicle Model:

The protocol of the HAP-pellicle model involves the development of apellicle on hydroxyapatite (HAP) powder to simulate pellicle coveredteeth. The procedure starts by incubating 10 mg of HAP powder withpooled parotid saliva at 35 C for 1 hour. The saliva is removed aftercentrifugation and the prepared HAP powder is treated with CPC solution(positive control), water (negative control) or CPC test rinse solutionfor 1 minute in the presence of saliva. Each treatment solution(controls and test) is removed after centrifugation. The HAP residue iswashed with saliva for 1 minute and removed after centrifugation. It isthen treated with tea solution for 1 minute. The tea solution is thenremoved from the treated HAP after centrifugation. The treated HAP iswashed with saliva as described earlier. 2 additional cycles oftreatment are carried out. After 3 cycles of treatment, the HAP isdissolved and absorbance read from 350-550 nm. The AUC (Area Under theCurve) of absorbance between 350-550 nm is the measure of stain. Eachtest set is run in triplicate.

Bovine Tooth Model

This model utilizes extracted bovine teeth which have been mounted onpolyacrylic material. Bovine tooth are first bleached with diluteperoxide followed by washing with water. The bleached teeth areincubated with saliva for 4 hours and then dried. The teeth are thenimaged to get baseline color values (L*a*b*), using digital photographyusing the white light imaging system (Fuji 2000 Camera). The teeth arethen incubated in saliva for 18 hours to generate a mature pelliclecoating. The saliva is then removed and the teeth are treated with adentifrice slurry (containing no antimicrobials) for 2 minutes. Thedentifrice slurry is removed and the teeth are washed with water for 1minute. The teeth specimens are now ready for treatment. Teeth specimensare treated with CPC solution (positive control), water (negativecontrol) or CPC test rinse solution for 1 minute in the presence ofsaliva. The teeth are then incubated with saliva for 20 minutes at 35°C. Each specimen is subsequently treated with a freshly made teasolution for 15 minutes, followed by another washing and incubation withsaliva for 20 minutes. A total of 6 treatment cycles are carried out.After 6 cycles, the teeth are dried and L*a*b* values are measured usingphoto imaging. L* represents lightness on the y axis, a* representschroma (red-green) on the x axis, and b* represents chroma (yellow-blue)on the z axis. Changes in the individual L*, a*, and b* components (Δvalues) are calculated by subtracting the L*a*b* measurements of treatedteeth from the L*a*b* measurements of untreated and unstained teeth. Thetotal color change (ΔE) is calculated as the square root of the sum ofthe square of the Δ values. All tests are carried out with a replicateof four teeth.

B. Evaluation of Anti-Staining Activity of Aldehydes, Ketones andAnionic Agents

Mouth rinse formulations were evaluated in the bovine tooth modeldescribed above. The treatment composition contained 0.07% CPC asantimicrobial and anisaldehyde, anionic chelant or combinations asanti-staining agent. The base composition containing 0.07% CPC withoutanti-staining agent was the positive (staining) control and water wasthe negative (non-staining) control. Results are shown below.

% Reduction in Treatment Group stain (normalized) 0.07% CPC Base 0.00Base + 0.1% Anisaldehyde 24.20 Base + 0.15% TK Pyrophosphate 30.08Base + 0.1% CM Dextran 31.18 Base + 0.1% Anisaldehyde/0.15% TK Pyro95.62 Base + 0.1% Anisaldehyde/0.1% CM Dextran 81.11 Water 100.00

These results demonstrate that each of the agents used alone providereduction of stain. Surprisingly, there was synergy on the combinationof anisaldehyde with either CM dextran or tetrapotassium pyrophosphate(TKPP) in reducing or nearly eliminating staining Importantly, thebioavailability of the CPC in the rinse formulations as measured usingin vitro Disk Retention Assay (DRA) was between 80-100%, indicating thatthe anti-stain additives did not significantly affect CPCbioavailability. The DRA method is described in commonly assignedapplication WO 05/072693 and in S. J. Hunter-Rinderle, et al.,“Evaluation of Cetylpyridinium Chloride-Containing Mouthwashes Using InVitro Disk Retention and Ex Vivo Plaque Glycolysis Methods,” J. Clin.Den., 1997, 8:107-113. These assays are recommended for use in theproposed OTC monograph (Federal Register Vol. 68, No. 103 Part 356,“Oral Health Care Drug Products For Over-The-Counter Human Use;Antigingivitis/Antiplaque Drug Products; Establishment of a Monograph:Proposed Rules”). This method is designed as a performance assay toanalyze mouth rinse formulations containing from about 0.03% to about0.1% CPC to quantitatively determine the “free” (“unbound”) or“bioavailable” level of CPC needed for clinical efficacy. The DRAmeasures the amount of CPC “binding” to standardized cellulose filterdisks during filtration of an undiluted mouth rinse sample. The“bioavailable” CPC binds to the hydroxyl groups on the cellulose fiberduring filtration while CPC, which has been rendered “non-bioavailable”(or “bound”)” through interactions with mouth rinse components, simplypasses through the filter paper, i.e., the positive charge on thecompound is no longer available for binding to the negatively chargedcellulose disks. In this way, the DRA test provides an estimate of theamount of CPC available for activity, i.e., binding to bacteria andmucosal surfaces, during use of the mouth rinse. DRA measurements of CPCavailability have been positively correlated to results of in vitromicrobiological assays and in vivo germ kill tests. Historically,cellulose fibers have been used in other applications to similarlymonitor biological activity of drug actives (“Dairy Products” inOfficial Methods of Analysis of the Association of Chemical AnalyticalChemists. 13^(th) ed., 1980, Chapter 16:256). The method has beenvalidated and shown to perform with acceptable accuracy, precision, andselectivity.

Mouth rinse formulations comprising from about 0.035 to about 0.1% CPCwould pass the DRA test if assay results show the level of bioavailableCPC to be ≥324 ppm. For example, a formulation comprising 0.05% CPC at72% bioavailability would provide 360 ppm CPC. Testing of productscontaining bioavailable levels of CPC of ≥324 ppm demonstrates positiveclinical (antigingivitis, antiplaque) outcomes. Determination of CPCbioavailability in a finished product is important to productperformance as it readily defines the amount (concentration) of activeavailable for deposition at the site of action. Because the positivelycharged (cationic) hydrophilic region is critical to antimicrobialactivity, any formulation component that diminishes the activity of thiscationic group or that competes with the group may inactivate theproduct. Desirably, a formulation containing 0.05% CPC would have atleast about 65% bioavailability to deliver at least about 324 ppmbioavailable CPC. A formulation containing a lower level of CPC such as0.04% would need to have at least about 81% bioavailability to deliverthe minimum required level of bioavailable CPC for antigingivitisefficacy. Depending upon the particular application and theconcentration of CPC or other quaternary ammonium agent, about 50%bioavailability may be acceptable.

Chemical structure activity modeling of stain reduction data (using theHAP saliva pellicle model to evaluate mouth rinses containing 0.07%cetylpyridinium chloride) was carried out. Water was used as thenegative control and 0.07% solution of cetylpyridinium chloride was thepositive control.

The data set was used to develop a Structural Activity Relationship(SAR) model to correlate the observed reduction of stain to specificchemical structural features of test compounds. The best regressionequation was determined and further used to predict % reduction of stainfor other chemical ingredients. In order to develop the QSAR(Quantitative Structural Activity Relationship), the % reduction ofstain as determined by the above experiment at 0.1% anti-stain activeconcentration was used in the CaChe 7.1 molecular modeling programmefrom Fujitsu Limited. The % Reduction of Stain from a training set of 15chemical samples was used to calculate the Complete Quantum QSAR. TheCAChe MOPAC (Molecular Orbital Package) application determines both anoptimum geometry and the electronic properties of molecules by solvingthe Schrödinger equation using the semi-empirical Hamiltonians AM1, PM3and PMS, developed by M. J. S. Dewar and J. J. P. Stewart. [See J. Am.Chem. Soc. (1985), 107, 3902; J. Comput. Chem. (1989), 10, 209; MOPAC2002, (1999).] The following regression equation, which is the best from50803424 possible triple combinations of 674 descriptors, gave thehighest r{circumflex over ( )}2=0.8849.

% Reduction in stain from CPH=−0.2535*(Carboncount)²−15.9064*sqrt(donatable hydrogen count)−956.4721*1.0/[cuberoot(bonded gravitational index)]+130.7168

The cross-validated correlation coefficient (cvr²=0.7998) suggests thatthe stability of the equation on addition of similar training data islikely to be reasonable as it is above 0.70. Eq. 1 below calculates thebonded gravitational index (G₁) over all bonded atoms i, j in themolecule, which reflects the effective mass distribution in the moleculeand effectively describes the molecular dispersion forces in the bulkliquid media.

G ₁=Σ_(ij) ^(over all bonded atoms)(m _(i) m _(j) /r _(ij) ²)  Eq. 1

In the above equations, carbon count=total number of carbon atoms in themolecule, donatable hydrogen count=number of hydrogen atoms in amolecule that has labile H atoms (such as in OH, COOH and NH₂ groups),m_(i) and m_(j)=the atomic masses of the bonded atoms, andr_(ij)=respective bond lengths.

Based on the above model, the predicted Normalized % Stain Reductionvalues of many other reactive carbonyl compounds are listed below. Thesecompounds have a predicted stain reduction that is comparable toanisaldehyde. The stain reduction from 0.07% CPC solution (positivecontrol) was normalized with water having stain reduction of 100%, i.e.,produced no stain. Preferred among the agents listed below are thosehaving a % normalized stain reduction value of at least about 10%, atleast about 20%, at least about 30% or at least about 40%. Agents havingbelow about 10% stain reduction in this model are predicted to haveminimal performance.

Active Normalized % Stain Reduction heliotropin 82.87 veratraldehyde70.35 3-methyl-1,2-cyclopentadione 55.33 anisaldehyde 54.93 phenethylformate 54.77 acetophenone 40.46 phenylacetaldehyde 40.034-methylacetophenone 37.07 p-Tolu acetaldehyde 36.65 Isophorone 33.95gamma-undecalactone 31.87 ρ-methyl cinnamaldehyde 30.58 benzylacetone29.55 octanal 28.84 (-) piperitone 28.70 perillaldehyde 27.58cuminaldehyde 26.80 α-methyl cinnamaldehyde 26.49 isomenthone 26.03menthone 26.00 carvone 23.64 decanal 20.78 maltol 20.24p-Isopropylphenylacetaldehyde 19.37 trans-citral 17.81 dihydrojasmone17.56 beta-napthylmethyl ketone 13.15 tiglic aldehyde 8.85 ethylvanillin 7.03 isovaleraldehyde 6.39

Using chemical structure activity modeling described above and theBovine tooth Model, the following anionic compounds are anticipated tohave similar anti-staining activity as carboxymethyl dextran andtetrapotassium pyrophosphosphate. These compounds contain anionicphosphate, carboxy or sulfate groups, are at least slightly watersoluble or water-dispersible and are used in the acid form or as alkalimetal or ammonium salts thereof. Preferred anionic agents are thosehaving a % normalized stain reduction value of at least about 10%, atleast about 20%, at least about 30% or at least about 40%.

Active Normalized % stain reduction tetra potassium pyrophosphate 55.15phytic acid 42.99 D-fructose-1-6-biphosphate 41.83 dihydroxyacetonephosphate 40.70 D-Erythrose-4-phosphate 34.40 Glycerol phosphate 33.43creatine phosphate 30.70 D-ribose-5-phosphate 28.31D-fructose-6-phosphate 28.16 D-xylose-5-phosphate 24.73glyceraldehyde-3-phosphate 22.66 α-D-glucose-6-phosphate 15.65α-D-glucose-1-phosphate 15.52 uridine-5-phosphate 11.37 ascorbylphosphate 11.35 Xylitol-5-phosphate 8.01 DL malic acid 6.61

The following polymeric materials are anticipated to have anti-stainingactivity: dextran sulfate; lower molecular weight polymers (about 15,000or less) such as carboxymethyl hydroxypropylcellulose, carboxymethylmethylcellulose; acrylic-maleic acid copolymers; and carboxymethylstarch. Polymers having a low charge density are preferred. Examplesinclude lightly charged carboxylated, phosphated or sulfated watersoluble polymers such as celluloses, dextrans, starches and the likewith a degree of anionic group substitution (DS) of 0.2 or less. DS of0.2 is defined as 2 anionic group substituent units (e.g.,carboxymethyl, phosphate or sulfate) per 10 repeating units in thepolymer, e.g., glucose units in cellulose). By “water soluble polymers”herein is meant to include polymers that are solvatable or hydratablewith water forming transparent, translucent, or semi-opaque solutions orgels, which are generally accepted as uniformly dispersed in water or ina predominately water containing medium. It is known that water solublepolymers do not necessarily form “true” solutions but can exist ashydrated particles that are fully or partially solvated and uncoiled.

A lower molecular weight of the polymer is preferred as lower viscositybuild in the formulation may be desired. For example, for a mouth rinseformulation the desired viscosity is about 1 to 5 cP. Furthermore, it isbelieved that the lower molecular weight polymers can better interactwith the salivary proteins and partition into one another better. Athigher molecular weights (>15,000), the protein would interact with anentangled polymer network rather than identifiable polymer strands orcoils and the protein partition coefficient would become independent ofmolecular weight. The anionic polymers useful herein would have averagemolecular weight (MW) of about 15,000 or less, about 10,000 or less orabout 5000 or less.

C. Evaluation of Anti-Staining Activity of Nonionic EthoxylatedSurfactants (Ethoxylates)

The staining potential of an emulsion rinse containing 0.1% CPC and 0.3%flavor oil was evaluated using 0.05% of a nonionic ethoxylated linearalcohol surfactant (available under the tradename Performathox 490 fromBaker Hughes, MW=4522; HLB 18), having the following general structure.Staining results as evaluated by the bovine tooth model are as follows.

Group Group delta E % Stain Reduction 0.07% CPC 19.02 0.0 0.07% CPC +0.05% 15.92 43.7 Performathox 490 Water 11.94 100.0

The HAP-pellicle model was used to evaluate ethoxylates of differentcarbon chain lengths, EO units, EO weight %, HLB and molecular weightsfor stain reduction when incorporated at different concentrations in anemulsion rinse containing 0.1% CPC as described in co-filed patentapplication entitled MOUTH RINSE EMULSIONS. Results are summarized inTable 1 below. A positive # for Normalized Stain Reduction from baserinse indicates a reduction in stain while a negative number indicatesincreased staining. Modeling of the resultant data set indicates thatethoxylated alcohols having 18 or more carbons in the alcohol chain,about 35 or more EO (ethylene oxide) units and molecular weight betweenabout 2,000 to about 15,000 would provide a benefit in stain reductionwithout compromising bioavailability of CPC. Preferred for use hereinare ethoxylates having about 25 to 55 carbons in the alcohol chain, from50 to 100 EO units and MW between about 2,000 to about 5,000.

TABLE 1 Evaluation of Anti-Stain Performance of Ethoxylates # % EONormalized Carbons # EO by Mol. % Stain Material (tail) Units Wt. HLBWt. Polymer Reduction DRA Sigma 458988 34 10 50 10 920 0.05 −64.61 95.09Sigma 458988 34 10 50 10 920 0.1 −85.81 93.98 Sigma 458988 34 10 50 10920 0.2 −95.58 91.71 Brij 30 (Brij L4) 12 4 51 9.7 362 0.05 −42.95 90.99Brij 30 (Brij L4) 12 4 51 9.7 362 0.1 −64.30 80.98 Brij 30 (Brij L4) 124 51 9.7 362 0.2 −88.15 71.78 Brij 98 (Brij O 20) 18 20 78 18 1150 0.05−18.95 86.95 Brij 98 (Brij O 20) 18 20 78 18 1150 0.1 12.25 71.79 Brij98 (Brij O 20) 18 20 78 18 1150 0.2 46.61 62.87 Performathox 450 34 1050 10 920 0.05 −23.37 91.5 Performathox 450 34 10 50 10 920 0.1 −33.7384.3 Performathox 450 34 10 50 10 920 0.15 −37.57 81.4 Performathox 45034 10 50 10 920 0.2 −45.31 75.5 Performathox 480 34 40 80 16 2300 0.056.39 90.1 Performathox 480 34 40 80 16 2300 0.1 19.09 82.1 Performathox480 34 40 80 16 2300 0.15 33.96 74.8 Performathox 480 34 40 80 16 23000.2 26.02 71.8 Performathox 490 40 90 90 18 4522 0.05 13.68 86.2Performathox 490 40 90 90 18 4522 0.1 18.77 80.9 Performathox 490 40 9090 18 4522 0.15 43.37 75.9 Performathox 490 40 90 90 18 4522 0.2 32.7172.6 Performathox 750 50 16 50 10 1400 0.05 −51.84 96.3 Performathox 75050 16 50 10 1400 0.1 −41.43 93.4 Performathox 750 50 16 50 10 1400 0.15−72.63 92.2 Performathox 750 50 16 50 10 1400 0.2 −92.81 88.6 Brij S10018 100 94 18.8 4654 0.05 19.82 85.5 Brij S100 18 100 94 18.8 4654 0.119.82 78.7 Brij S100 18 100 94 18.8 4654 0.15 26.57 74.4 Brij S100 18100 94 18.8 4654 0.2 34.76 71.7

The total amount of anti-stain agent included in the presentcompositions will be from about 0.01% to about 5%, from about 0.025% toabout 3% or from about 0.1% to about 2%. The anti-stain agents will beat least slightly water-soluble (about 0.1% solubility at 25° C.,preferably higher) or be water-dispersible for optimum interaction withsalivary proteins and the cationic antimicrobial agent.

Cationic Antimicrobial Agents

Cationic antimicrobial agents that are known for their propensity toinduce tooth staining include quaternary ammonium salts, bis-biquanidesalts; and metal ion sources that provide metal ions such as stannous,zinc and copper. These cationic agents provide effectiveness in killing,and/or altering metabolism, and/or suppressing the growth of,microorganisms which cause topically-treatable infections and diseasesof the oral cavity, such as plaque, caries, gingivitis, and periodontaldisease. The level of antimicrobial agent is dependent on the type ofantimicrobial agent and other factors and typically will be from about0.01% to about 5.0%, by weight of the composition.

The quaternary ammonium compounds in the compositions of the presentinvention include those in which one or two of the substitutes on thequaternary nitrogen has a carbon chain length (typically alkyl group)from about 8 to about 20, typically from about 10 to about 18 carbonatoms while the remaining substitutes (typically alkyl or benzyl group)have a lower number of carbon atoms, such as from about 1 to about 7carbon atoms, typically methyl or ethyl groups. Cetylpyridiniumchloride, cetyl pyridinium fluoride, tetradecylpyridinium chloride,N-tetradecyl-4-ethyl pyridinium chloride, domiphen bromide, benzalkoniumchloride, benzethonium chloride, methyl benzethonium chloride, dodecyltrimethyl ammonium bromide, dodecyl dimethyl (2-phenoxyethyl) ammoniumbromide, benzyl dimethoxystearyl ammonium chloride, quaternized5-amino-1,3-bis(2-ethyl-hexyl)-5-methyl hexa hydropyrimidine, lauryltrimethylammonium chloride, cocoalkyl trimethylammonium chloride, cetyltrimethylammonium bromide,di-isobutylphenoxyethyl-dimethylbenzylammonium chloride, dodecyltrimethyl ammonium bromide, are exemplary of typical quaternary ammoniumantimicrobial agents. Other compounds are bis[4-(R-amino)-1-pyridinium]alkanes as disclosed in U.S. Pat. No. 4,206,215 to Bailey. Thepyridinium compounds are the preferred quaternary ammonium compounds,particularly preferred being cetylpyridinium, or tetradecylpyridiniumhalide salts (i.e., chloride, bromide, fluoride and iodide).Particularly preferred are cetylpyridinium chloride and fluoride salts.The quaternary ammonium antimicrobial agents are included in the presentinvention at levels of at least about 0.025 or at least about 0.035% orat least about 0.045% to about 1.0%, or from about 0.025% to about 0.1%by weight of the composition.

The present compositions may comprise a metal ion source that providesstannous ions, zinc ions, copper ions, or mixtures thereof asantimicrobial agent. The metal ion source can be a soluble or asparingly soluble compound of stannous, zinc, or copper with inorganicor organic counter ions. Examples include the fluoride, chloride,chlorofluoride, acetate, hexafluorozirconate, sulfate, tartrate,gluconate, citrate, malate, glycinate, pyrophosphate, metaphosphate,oxalate, phosphate, carbonate salts and oxides of stannous, zinc, andcopper.

Stannous, zinc and copper ions have been found to help in the reductionof gingivitis, plaque, sensitivity, and improved breath benefits. Thecomposition may comprise from about 50 ppm to about 20,000 ppm metal ionof the total composition, from about 500 ppm to about 15,000 ppm or fromabout 3,000 ppm to about 10,000 ppm. This is the total amount of metalions (stannous, zinc, copper and mixtures thereof) for delivery to thetooth surface.

Dentifrices containing stannous salts, such as stannous fluoride andstannous chloride, are described in U.S. Pat. No. 5,004,597 to Majeti etal. Other descriptions of stannous salts and ingredients needed tostabilize the stannous are found in U.S. Pat. No. 5,578,293 issued toPrencipe et al. and in U.S. Pat. No. 5,281,410 issued to Lukacovic etal.

Stannous salts useful herein include stannous fluoride and stannouschloride dihydrate, stannous acetate, stannous tartrate and sodiumstannous citrate. Examples of suitable zinc ion sources are zinc oxide,zinc sulfate, zinc chloride, zinc citrate, zinc lactate, zinc gluconate,zinc malate, zinc tartrate, zinc carbonate, zinc phosphate, and othersalts listed in U.S. Pat. No. 4,022,880. Examples of suitable copper ionsources are listed in U.S. Pat. No. 5,534,243 and include the chloride,sulfate gluconate, and glycinate salts. The combined metal ion sourceswill typically be present in an amount of from about 0.05% to about 11%,by weight of the final composition, from about 0.5 to about 7%, or fromabout 1% to about 5%. The stannous salts will typically be present in anamount of from about 0.1 to about 7%, from about 1% to about 5%, or fromabout 1.5% to about 3% by weight of the total composition. The amount ofzinc or copper salts will typically range from about 0.01 to about 5%,from about 0.05 to about 4%, or from about 0.1 to about 3.0%. Preferredmetal ion sources include stannous fluoride, stannous chloride, stannouschloride dihydrate, zinc citrate, zinc lactate, zinc sulfate, zincchloride, zinc acetate, zinc oxide, copper sulfate, and coppergluconate.

Additional Antimicrobial Agents

The present compositions may additionally comprise otherorally-effective antimicrobial agents including non-cationic agents suchas halogenated diphenyl ethers, phenolic compounds including phenol andits homologs, mono and poly-alkyl and aromatic halophenols, resorcinoland its derivatives, bisphenolic compounds and halogenatedsalicylanilides, benzoic esters, and halogenated carbanilides, essentialoils; enzymes such as endoglycosidase, papain, dextranase, mutanase, andmixtures thereof. The level of other antimicrobial agent will alsodepend on the type of antimicrobial agent and other factors andtypically will be from about 0.01% to about 5.0%, by weight of thecomposition.

Antimicrobially-effective essential oils include one or more offlavor/fragrance chemicals such as citral, neral, geranial, geraniol,nerol, eucalyptol, eugenol, eugenyl acetate, carvacrol, thymol,o-cymen-5-ol (isopropylmethylphenol, IPMP), farnesol, benzyl alcohol,benzaldehyde, hinokitiol (isopropyltropolone), terpinene-4-ol,zingerone, allyl isothiocyanate, dipentene, α-pinene, β-pinene, menthol,methyl salicylate, anethole, carvone, limonene, ocimene, n-decylalcohol, citronellal, citronellol, methyl acetate, citronellyl acetate,methyl eugenol, linalool, ethyl linalool, camphor, safrole,chlorothymol, guaiacol, phenol, phenyl salicylate, cinnamic acid,guaiacol, isoeugenol, dihydroeugenol, vanillyl butyl ether,5-propenylguaethol, 4-ethyl-2-methoxyphenol, 4-allyl-2-methoxyphenolacetate, and 4-methyl guaiacol. Natural sources of these chemicals maybe used. The selection of the essential oils to is based ondemonstration of their activity against microorganisms known to beinvolved in undesirable oral cavity conditions such as gingivitis,periodontal disease and oral malodor. For example, useful herein is ablend of essential oils comprising at least two components, a firstcomponent selected from acyclic or non-ring structures such as citral,neral, geranial, geraniol, nerol or derivatives thereof and a secondcomponent selected from ring-containing structures such as eucalyptol,eugenol, carvacrol or derivatives thereof. These essential oil blendsare described in commonly-assigned patent application published asUS20080253976A1. The essential oil blend is used at a level of at leastabout 0.02% by weight of the composition to provide effectiveantimicrobial activity.

A number of the above antimicrobially effective essential oil chemicalsare aldehydes and ketones which are useful as anti-stain agents.

In addition to the components described above, the present compositionsmay comprise additional optional components collectively referred to asorally acceptable carrier materials, which are described in thefollowing paragraphs.

Orally Acceptable Carrier Materials

The orally acceptable carrier materials comprise one or more compatiblesolid or liquid excipients or diluents which are suitable for topicaloral administration. By “compatible,” as used herein, is meant that thecomponents of the composition are capable of being commingled withoutinteraction in a manner which would substantially reduce thecomposition's stability and/or efficacy. In particular, the carriermaterials should not have a negative effect on the bioavailability ofthe cationic antimicrobials or on the anti-staining activity of theanti-stain agents used herein.

The carriers or excipients of the present invention can include theusual and conventional components of dentifrices, non-abrasive gels,subgingival gels, mouthwashes or rinses, mouth sprays, chewing gums,lozenges and breath mints as more fully described hereinafter.

The choice of a carrier to be used is basically determined by the waythe composition is to be introduced into the oral cavity. Carriermaterials for toothpaste, tooth gel or the like include abrasivematerials, sudsing agents, binders, humectants, flavoring and sweeteningagents, etc. as disclosed in e.g., U.S. Pat. No. 3,988,433 to Benedict.Carrier materials for biphasic dentifrice formulations are disclosed inU.S. Pat. No. 5,213,790, issued May 23, 1993, U.S. Pat. Nos. 5,145,666,and 5,281,410 all to Lukacovic et al. and in U.S. Pat. Nos. 4,849,213and 4,528,180 to Schaeffer. Mouthwash, rinse or mouth spray carriermaterials typically include water, flavoring and sweetening agents,etc., as disclosed in, e.g., U.S. Pat. No. 3,988,433 to Benedict.Lozenge carrier materials typically include a candy base; chewing gumcarrier materials include a gum base, flavoring and sweetening agents,as in, e.g., U.S. Pat. No. 4,083,955 to Grabenstetter et al. Sachetcarrier materials typically include a sachet bag, flavoring andsweetening agents. For subgingival gels used for delivery of activesinto the periodontal pockets or around the periodontal pockets, a“subgingival gel carrier” is chosen as disclosed in, e.g. U.S. Pat. Nos.5,198,220 and 5,242,910 both to Damani. Carriers suitable for thepreparation of compositions of the present invention are well known inthe art. Their selection will depend on secondary considerations liketaste, cost, and shelf stability, etc.

The compositions of the present invention may also be in the form ofnon-abrasive gels and subgingival gels, which may be aqueous ornon-aqueous. In still another aspect, the invention provides a dentalimplement impregnated with the present composition. The dental implementcomprises an implement for contact with teeth and other tissues in theoral cavity, said implement being impregnated with the presentcomposition. The dental implement can be impregnated fibers includingdental floss or tape, chips, strips, films and polymer fibers.

In one embodiment, the compositions of the subject invention are in theform of dentifrices, such as toothpastes, tooth gels and tooth powders.Components of such toothpaste and tooth gels generally include one ormore of a dental abrasive (from about 6% to about 50%), a surfactant(from about 0.5% to about 10%), a thickening agent (from about 0.1% toabout 5%), a humectant (from about 10% to about 55%), a flavoring agent(from about 0.04% to about 2%), a sweetening agent (from about 0.1% toabout 3%), a coloring agent (from about 0.01% to about 0.5%) and water(from about 2% to about 45%). Such toothpaste or tooth gel may alsoinclude one or more of an anticaries agent (from about 0.05% to about0.3% as fluoride ion) and an anticalculus agent (from about 0.1% toabout 13%). Tooth powders, of course, contain substantially allnon-liquid components.

Other embodiments of the subject invention are liquid products,including mouthwashes or mouth rinses, mouth sprays, dental solutionsand irrigation fluids. Components of such mouthwashes and mouth spraystypically include one or more of water (from about 45% to about 95%),ethanol (from about 0% to about 25%), a humectant (from about 0% toabout 50%), a surfactant (from about 0.01% to about 7%), a flavoringagent (from about 0.04% to about 2%), a sweetening agent (from about0.1% to about 3%), and a coloring agent (from about 0.001% to about0.5%). Such mouthwashes and mouth sprays may also include one or more ofan anticaries agent (from about 0.05% to about 0.3% as fluoride ion) andan anticalculus agent (from about 0.1% to about 3%). Components ofdental solutions generally include one or more of water (from about 90%to about 99%), preservative (from about 0.01% to about 0.5%), thickeningagent (from 0% to about 5%), flavoring agent (from about 0.04% to about2%), sweetening agent (from about 0.1% to about 3%), and surfactant(from 0% to about 5%).

Types of orally acceptable carrier materials or excipients, which mayoptionally be included in compositions of the present invention, alongwith specific non-limiting examples, are described in the followingparagraphs.

Desensitizing Agent

The present compositions may optionally contain a dentinal desensitizingagent such as salts of potassium, calcium, strontium and tin includingnitrate, chloride, fluoride, phosphates, pyrophosphate, polyphosphate,citrate, oxalate and sulfate.

Anticalculus Agent

The present compositions may optionally include an anticalculus agent,such as a pyrophosphate salt as a source of pyrophosphate ion. Thepyrophosphate salts useful in the present compositions include thedialkali metal pyrophosphate salts, tetraalkali metal pyrophosphatesalts, and mixtures thereof. Disodium dihydrogen pyrophosphate(Na₂H₂P₂O₇), tetrasodium pyrophosphate (Na₄P₂O₇), and tetrapotassiumpyrophosphate (K₄P₂O₇) in their unhydrated as well as hydrated forms arethe preferred species. In compositions of the present invention, thepyrophosphate salt may be present in one of three ways: predominatelydissolved, predominately undissolved, or a mixture of dissolved andundissolved pyrophosphate.

Compositions comprising predominately dissolved pyrophosphate refer tocompositions where at least one pyrophosphate ion source is in an amountsufficient to provide at least about 1.0% free pyrophosphate ions. Theamount of free pyrophosphate ions may be from about 1% to about 15%,from about 1.5% to about 10% in one embodiment, and from about 2% toabout 6% in another embodiment. Free pyrophosphate ions may be presentin a variety of protonated states depending on the pH of thecomposition.

Compositions comprising predominately undissolved pyrophosphate refer tocompositions containing no more than about 20% of the totalpyrophosphate salt dissolved in the composition, or less than about 10%of the total pyrophosphate dissolved in the composition. Tetrasodiumpyrophosphate salt is a preferred pyrophosphate salt in thesecompositions. Tetrasodium pyrophosphate may be the anhydrous salt formor the decahydrate form, or any other species stable in solid form inthe dentifrice compositions. The salt is in its solid particle form,which may be its crystalline and/or amorphous state, with the particlesize of the salt preferably being small enough to be aestheticallyacceptable and readily soluble during use. The amount of pyrophosphatesalt useful in making these compositions is any tartar control effectiveamount, generally from about 1.5% to about 15%, from about 2% to about10%, or from about 3% to about 8%, by weight of the dentifricecomposition.

Compositions may also comprise a mixture of dissolved and undissolvedpyrophosphate salts. Any of the above mentioned pyrophosphate salts maybe used.

The pyrophosphate salts are described in more detail in Kirk-OthmerEncyclopedia of Chemical Technology, Third Edition, Volume 17,Wiley-Interscience Publishers (1982).

Optional agents to be used in place of or in combination with thepyrophosphate salt include such known materials as synthetic anionicpolymers, including polyacrylates and copolymers of maleic anhydride oracid and methyl vinyl ether (e.g., Gantrez), as described, for example,in U.S. Pat. No. 4,627,977, to Gaffar et al., as well as, e.g.,polyamino propane sulfonic acid (AMPS), diphosphonates (e.g., EHDP;AHP), polypeptides (such as polyaspartic and polyglutamic acids), andmixtures thereof.

Fluoride Ion Source

It is common to have a water-soluble fluoride compound present indentifrices and other oral compositions in an amount sufficient to givea fluoride ion concentration in the composition, and/or when it is usedof from about 0.0025% to about 5.0% by weight or from about 0.005% toabout 2.0% by weight, to provide anticaries effectiveness. A widevariety of fluoride ion-yielding materials can be employed as sources ofsoluble fluoride in the present compositions. Examples of suitablefluoride ion-yielding materials are found in U.S. Pat. No. 3,535,421,Oct. 20, 1970 to Briner et al. and U.S. Pat. No. 3,678,154, Jul. 18,1972 to Widder et al. Representative fluoride ion sources include:stannous fluoride, sodium fluoride, potassium fluoride, sodiummonofluorophosphate, indium fluoride, amine fluoride and many others.Stannous fluoride and sodium fluoride are among preferred sources, aswell as mixtures thereof.

Abrasives

Dental abrasives useful in the compositions of the subject inventioninclude many different materials. The material selected must be onewhich is compatible within the composition of interest and does notexcessively abrade dentin. Suitable abrasives include, for example,silicas including gels and precipitates, insoluble sodiumpolymetaphosphate, hydrated alumina, calcium carbonate, dicalciumorthophosphate dihydrate, calcium pyrophosphate, tricalcium phosphate,calcium polymetaphosphate, and resinous abrasive materials such asparticulate condensation products of urea and formaldehyde.

Another class of abrasives for use in the present compositions is theparticulate thermo-setting polymerized resins as described in U.S. Pat.No. 3,070,510 issued to Cooley and Grabenstetter. Suitable resinsinclude, for example, melamines, phenolics, ureas, melamine-ureas,melamine-formaldehydes, urea-formaldehyde, melamine-urea-formaldehydes,cross-linked epoxides, and cross-linked polyesters.

Silica dental abrasives of various types are preferred because of theirunique benefits of exceptional dental cleaning and polishing performancewithout unduly abrading tooth enamel or dentine. The silica abrasivepolishing materials herein, as well as other abrasives, generally havean average particle size ranging between about 0.1 to about 30 microns,and preferably from about 5 to about 15 microns. The abrasive can beprecipitated silica or silica gels such as the silica xerogels describedin Pader et al., U.S. Pat. No. 3,538,230 and DiGiulio, U.S. Pat. No.3,862,307. Examples include the silica xerogels marketed under the tradename “Syloid” by the W.R. Grace & Company, Davison Chemical Division andprecipitated silica materials such as those marketed by the J. M. HuberCorporation under the trade name, Zeodent®, particularly the silicascarrying the designation Zeodent® 119, Zeodent® 118, Zeodent® 109 andZeodent® 129. The types of silica dental abrasives useful in thetoothpastes of the present invention are described in more detail inWason, U.S. Pat. No. 4,340,583; and in commonly-assigned U.S. Pat. Nos.5,603,920; 5,589,160; 5,658,553; 5,651,958; and 6,740,311.

Mixtures of abrasives can be used such as mixtures of the various gradesof Zeodent® silica abrasives listed above. The total amount of abrasivein dentifrice compositions of the subject invention typically range fromabout 6% to about 70% by weight; toothpastes generally contain fromabout 10% to about 50% of abrasives, by weight of the composition.Dental solution, mouth spray, mouthwash and non-abrasive gelcompositions of the subject invention typically contain little or noabrasive.

Tooth Substantive Agent

The present invention may include a tooth substantive agent such aspolymeric surface active agents (PMSA's), which are polyelectrolytes,more specifically anionic polymers. The PMSA's contain anionic groups,e.g., phosphate, phosphonate, carboxy, or mixtures thereof, and thus,have the capability to interact with cationic or positively chargedentities. The “mineral” descriptor is intended to convey that thesurface activity or substantivity of the polymer is toward mineralsurfaces such as calcium phosphate minerals or teeth.

PMSA's are useful in the present compositions because of their stainprevention benefit. The PMSA's may provide a stain prevention benefitbecause of their reactivity or substantivity to mineral surfaces,resulting in desorption of portions of undesirable adsorbed pellicleproteins, in particular those associated with binding color bodies thatstain teeth, calculus development and attraction of undesirablemicrobial species. The retention of these PMSA's on teeth can alsoprevent stains from accruing due to disruption of binding sites of colorbodies on tooth surfaces.

The ability of PMSA's to bind stain promoting ingredients of oral careproducts, for example, stannous ions and cationic antimicrobials, isalso believed to be helpful. The PMSA will also provide tooth surfaceconditioning effects which produce desirable effects on surfacethermodynamic properties and surface film properties, which impartimproved clean feel aesthetics both during and most importantly,following rinsing or brushing. Many of these polymeric agents are alsoknown or expected to provide tartar control benefits when applied inoral compositions, hence providing improvement in both the appearance ofteeth and their tactile impression to consumers.

The polymeric mineral surface active agents include an agent which willhave a strong affinity for the tooth surface, deposit a polymer layer orcoating on the tooth surface and produce the desired surfacemodification effects. Suitable examples of such polymers arepolyelectrolytes such as condensed phosphorylated polymers;polyphosphonates; copolymers of phosphate- or phosphonate-containingmonomers or polymers with other monomers such as ethylenicallyunsaturated monomers and amino acids or with other polymers such asproteins, polypeptides, polysaccharides, poly(acrylate),poly(acrylamide), poly(methacrylate), poly(ethacrylate),poly(hydroxyalkylmethacrylate), poly(vinyl alcohol), poly(maleicanhydride), poly(maleate) poly(amide), poly(ethylene amine),poly(ethylene glycol), poly(propylene glycol), poly(vinyl acetate) andpoly(vinyl benzyl chloride); polycarboxylates and carboxy-substitutedpolymers; and mixtures thereof. Suitable polymeric mineral surfaceactive agents include the carboxy-substituted alcohol polymers describedin U.S. Pat. Nos. 5,292,501; 5,213,789, 5,093,170; 5,009,882; and4,939,284; all to Degenhardt et al. and the diphosphonate-derivatizedpolymers in U.S. Pat. No. 5,011,913 to Benedict et al; the syntheticanionic polymers including polyacrylates and copolymers of maleicanhydride or acid and methyl vinyl ether (e.g., Gantrez), as described,for example, in U.S. Pat. No. 4,627,977, to Gaffar et al. Diphosphonatemodified polyacrylic acid is another example. Polymers with activitymust have sufficient surface binding propensity to desorb pellicleproteins and remain affixed to enamel surfaces. For tooth surfaces,polymers with end or side chain phosphate or phosphonate functions arepreferred although other polymers with mineral binding activity mayprove effective depending upon adsorption affinity.

Additional examples of suitable phosphonate containing polymeric mineralsurface active agents include the geminal diphosphonate polymersdisclosed as anticalculus agents in U.S. Pat. No. 4,877,603 toDegenhardt et al; phosphonate group containing copolymers disclosed inU.S. Pat. No. 4,749,758 to Dursch et al. and in GB 1,290,724 (bothassigned to Hoechst) suitable for use in detergent and cleaningcompositions; and the copolymers and cotelomers disclosed as useful forapplications including scale and corrosion inhibition, coatings, cementsand ion-exchange resins in U.S. Pat. No. 5,980,776 to Zakikhani et al.and U.S. Pat. No. 6,071,434 to Davis et al. Additional polymers includethe water-soluble copolymers of vinylphosphonic acid and acrylic acidand salts thereof disclosed in GB 1,290,724 wherein the copolymerscontain from about 10% to about 90% by weight vinylphosphonic acid andfrom about 90% to about 10% by weight acrylic acid, more particularlywherein the copolymers have a weight ratio of vinylphosphonic acid toacrylic acid of 70% vinylphosphonic acid to 30% acrylic acid; 50%vinylphosphonic acid to 50% acrylic acid; or 30% vinylphosphonic acid to70% acrylic acid. Other suitable polymers include the water solublepolymers disclosed by Zakikhani and Davis prepared by copolymerizingdiphosphonate or polyphosphonate monomers having one or more unsaturatedC═C bonds (e.g., vinylidene-1,1-diphosphonic acid and2-(hydroxyphosphinyl)ethylidene-1,1-diphosphonic acid), with at leastone further compound having unsaturated C═C bonds (e.g., acrylate andmethacrylate monomers). Suitable polymers include thediphosphonate/acrylate polymers supplied by Rhodia under the designationITC 1087 (Average MW 3000-60,000) and Polymer 1154 (Average MW6000-55,000).

Suitable PMSA's will be stable and compatible with other components ofthe oral care composition such as ionic fluoride, cationicantimicrobials and metal ions, and are stable to hydrolysis in highwater content formulations, thus permitting a simple single phasedentifrice or mouth rinse formulation. If the PMSA does not have thesestability and compatibility properties, one option is a dual phaseformulation with the PMSA separated from the fluoride or otherincompatible component. Another option is to formulate non-aqueous,essentially non-aqueous or limited water compositions to minimizereaction between the PMSA and other components.

A preferred PMSA is a polyphosphate. A polyphosphate is generallyunderstood to consist of two or more phosphate molecules arrangedprimarily in a linear configuration, although some cyclic derivativesmay be present. Preferred polyphosphates are those having around threeor more phosphate groups so that surface adsorption at effectiveconcentrations produces sufficient non-bound phosphate functions, whichenhance the anionic surface charge as well as hydrophilic character ofthe surfaces. The polyphosphate salts desired include tripolyphosphate,tetrapolyphosphate and hexametaphosphate, among others. Polyphosphateslarger than tetrapolyphosphate usually occur as amorphous glassymaterials. Preferred in this invention are the linear polyphosphateshaving the formula: XO(XPO₃)_(n)X, wherein X is sodium, potassium orammonium and n averages from about 3 to about 125. Preferredpolyphosphates are those having n averaging from about 6 to about 21,such as those commercially known as Sodaphos (n≈6), Hexaphos (n≈13), andGlass H (n≈21) and manufactured by FMC Corporation and Astaris. Thesepolyphosphates may be used alone or in combination. Some polyphosphatesare susceptible to hydrolysis in high water formulations at acid pH,particularly below pH 5. Thus it is preferred to use longer-chainpolyphosphates, such as Glass H having an average chain length of about21. Such longer-chain polyphosphates when undergoing hydrolysis, produceshorter-chain polyphosphates which are still effective to deposit ontoteeth and provide a stain preventive benefit.

Other polyphosphorylated compounds may be used in addition to or insteadof the polyphosphate, in particular polyphosphorylated inositolcompounds such as phytic acid, myo-inositol pentakis(dihydrogenphosphate); myo-inositol tetrakis(dihydrogen phosphate), myo-inositoltrikis(dihydrogen phosphate), and an alkali metal, alkaline earth metalor ammonium salt thereof. Preferred herein is phytic acid, also known asmyo-inositol 1,2,3,4,5,6-hexakis (dihydrogen phosphate) or inositolhexaphosphoric acid, and its alkali metal, alkaline earth metal orammonium salts. Herein, the term “phytate” includes phytic acid and itssalts as well as the other polyphosphorylated inositol compounds.

The amount of tooth substantive agent may be from about 0.1% to about35% by weight of the total oral composition. In dentifrice formulations,the amount is typically from about 2% to about 30%, from about 5% toabout 25%, or from about 6% to about 20%. In mouth rinse compositions,the amount of tooth substantive agent is typically from about 0.1% to 5%or from about 0.5% to about 3%.

In addition to creating surface modifying effects, the tooth substantiveagent may also function to solubilize insoluble salts. For example,Glass H has been found to solubilize insoluble stannous salts. Thus, incompositions containing stannous fluoride for example, Glass Hcontributes to decreasing the stain promoting effect of stannous.

Chelating Agents

Another optional agent is a chelating agent, also called sequestrants,such as gluconic acid, tartaric acid, citric acid andpharmaceutically-acceptable salts thereof. Chelating agents are able tocomplex calcium found in the cell walls of the bacteria. Chelatingagents can also disrupt plaque by removing calcium from the calciumbridges which help hold this biomass intact. However, it is not desiredto use a chelating agent which has an affinity for calcium that is toohigh, as this may result in tooth demineralization, which is contrary tothe objects and intentions of the present invention. Suitable chelatingagents will generally have a calcium binding constant of about 10¹ to10⁵ to provide improved cleaning with reduced plaque and calculusformation. Chelating agents also have the ability to complex withmetallic ions and thus aid in preventing their adverse effects on thestability or appearance of products. Chelation of ions, such as iron orcopper, helps retard oxidative deterioration of finished products.

Examples of suitable chelating agents are sodium or potassium gluconateand citrate; citric acid/alkali metal citrate combination; disodiumtartrate; dipotassium tartrate; sodium potassium tartrate; sodiumhydrogen tartrate; potassium hydrogen tartrate; sodium, potassium orammonium polyphosphates and mixtures thereof. The amounts of chelatingagent suitable for use in the present invention will typically be fromabout 0.1% to about 2.5%, from about 0.5% to about 2.5%, or from about1.0% to about 2.5%.

Still other chelating agents suitable for use in the present inventionare the anionic polymeric polycarboxylates. Such materials are wellknown in the art, being employed in the form of their free acids orpartially or preferably fully neutralized water soluble alkali metal(e.g. potassium and preferably sodium) or ammonium salts. Examples are1:4 to 4:1 copolymers of maleic anhydride or acid with anotherpolymerizable ethylenically unsaturated monomer, preferably methyl vinylether (methoxyethylene) having a molecular weight (M.W.) of about 30,000to about 1,000,000. These copolymers are available for example asGantrez AN 139 (M.W. 500,000), AN 119 (M.W. 250,000) and S-97Pharmaceutical Grade (M.W. 70,000), of GAF Chemicals Corporation.

Other operative polymeric polycarboxylates include the 1:1 copolymers ofmaleic anhydride with ethyl acrylate, hydroxyethyl methacrylate,N-vinyl-2-pyrrolidone, or ethylene, the latter being available forexample as Monsanto EMA No. 1103, M.W. 10,000 and EMA Grade 61, and 1:1copolymers of acrylic acid with methyl or hydroxyethyl methacrylate,methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

Additional operative polymeric polycarboxylates are disclosed in U.S.Pat. Nos. 4,138,477 and 4,183,914 to Gaffar et al. and includecopolymers of maleic anhydride with styrene, isobutylene or ethyl vinylether; polyacrylic, polyitaconic and polymaleic acids; and sulfoacrylicoligomers of M.W. as low as 1,000 available as Uniroyal ND-2.

Surfactants

The present compositions may also comprise surfactants, also commonlyreferred to as sudsing agents. Suitable surfactants are those which arereasonably stable and foam throughout a wide pH range. The surfactantmay be anionic, nonionic, amphoteric, zwitterionic, cationic, ormixtures thereof.

Anionic surfactants useful herein include the water-soluble salts ofalkyl sulfates having from 8 to 20 carbon atoms in the alkyl radical(e.g., sodium alkyl sulfate) and the water-soluble salts of sulfonatedmonoglycerides of fatty acids having from 8 to 20 carbon atoms. Sodiumlauryl sulfate (SLS) and sodium coconut monoglyceride sulfonates areexamples of anionic surfactants of this type. Other suitable anionicsurfactants are sarcosinates, such as sodium lauroyl sarcosinate,taurates, sodium lauryl sulfoacetate, sodium lauroyl isethionate, sodiumlaureth carboxylate, and sodium dodecyl benzenesulfonate. Mixtures ofanionic surfactants can also be employed. Many suitable anionicsurfactants are disclosed by Agricola et al., U.S. Pat. No. 3,959,458,issued May 25, 1976. The present composition typically comprises ananionic surfactant at a level of from about 0.025% to about 9%, fromabout 0.05% to about 5% in some embodiments, and from about 0.1% toabout 1% in other embodiments.

Another suitable surfactant is one selected from the group consisting ofsarcosinate surfactants, isethionate surfactants and tauratesurfactants. Preferred for use herein are alkali metal or ammonium saltsof these surfactants, such as the sodium and potassium salts of thefollowing: lauroyl sarcosinate, myristoyl sarcosinate, palmitoylsarcosinate, stearoyl sarcosinate and oleoyl sarcosinate. Thesarcosinate surfactant may be present in the compositions of the presentinvention from about 0.1% to about 2.5% or from about 0.5% to about 2.0%by weight of the total composition.

Cationic surfactants useful in the present invention include derivativesof aliphatic quaternary ammonium compounds having one long alkyl chaincontaining from about 8 to 18 carbon atoms such as lauryltrimethylammonium chloride; cetyl pyridinium chloride; cetyltrimethylammonium bromide;di-isobutylphenoxyethyl-dimethylbenzylammonium chloride; cocoalkyltrimethylammonium chloride; cetyl pyridinium fluoride; etc. Thequaternary ammonium fluorides having detergent properties are describedin U.S. Pat. No. 3,535,421 to Briner et al. Certain cationic surfactantscan also act as germicides in the compositions disclosed herein.

Nonionic surfactants that can be used in the compositions of the presentinvention include compounds produced by the condensation of alkyleneoxide groups (hydrophilic in nature) with an organic hydrophobiccompound which may be aliphatic or alkylaromatic in nature. Examples ofsuitable nonionic surfactants include the Pluronics, polyethylene oxidecondensates of alkyl phenols, products derived from the condensation ofethylene oxide with the reaction product of propylene oxide and ethylenediamine, ethylene oxide condensates of aliphatic alcohols, long chaintertiary amine oxides, long chain tertiary phosphine oxides, long chaindialkyl sulfoxides and mixtures of such materials.

Zwitterionic synthetic surfactants useful in the present inventioninclude derivatives of aliphatic quaternary ammonium, phosphonium, andsulfonium compounds, in which the aliphatic radicals can be straightchain or branched, and wherein one of the aliphatic substituentscontains from about 8 to 18 carbon atoms and one contains an anionicwater-solubilizing group, e.g., carboxy, sulfonate, sulfate, phosphateor phosphonate.

Suitable betaine surfactants are disclosed in U.S. Pat. No. 5,180,577 toPolefka et al. Typical alkyl dimethyl betaines include decyl betaine or2-(N-decyl-N,N-dimethylammonio) acetate, coco betaine, myristyl betaine,palmityl betaine, lauryl betaine, cetyl betaine, cetyl betaine, stearylbetaine, etc. The amidobetaines are exemplified by cocoamidoethylbetaine, cocoamidopropyl betaine, lauramidopropyl betaine and the like.The betaines of choice include cocoamidopropyl betaines such aslauramidopropyl betaine.

Thickening Agents

In preparing toothpaste or gels, thickening agents are added to providea desirable consistency to the composition, to provide desirable activerelease characteristics upon use, to provide shelf stability, and toprovide stability of the composition, etc. Suitable thickening agentsinclude one or a combination of carboxyvinyl polymers, carrageenan,hydroxyethyl cellulose (HEC), natural and synthetic clays (e.g., Veegumand laponite) and water soluble salts of cellulose ethers such as sodiumcarboxymethylcellulose (CMC) and sodium carboxymethyl hydroxyethylcellulose. Natural gums such as gum karaya, xanthan gum, gum arabic, andgum tragacanth can also be used. Colloidal magnesium aluminum silicateor finely divided silica can be used as part of the thickening agent tofurther improve texture.

Suitable carboxyvinyl polymers useful as thickening or gelling agentsinclude carbomers which are homopolymers of acrylic acid crosslinkedwith an alkyl ether of pentaerythritol or an alkyl ether of sucrose.Carbomers are commercially available from B.F. Goodrich as the Carbopol®series, including Carbopol 934, 940, 941, 956, and mixtures thereof.

Thickening agents are typically present in an amount from about 0.1% toabout 15%, from about 2% to about 10%, or from about 4% to about 8%, byweight of the total toothpaste or gel composition, can be used. Higherconcentrations may be used for chewing gums, lozenges and breath mints,sachets, non-abrasive gels and subgingival gels.

Humectants

Another optional carrier material of the present compositions is ahumectant. The humectant serves to keep toothpaste compositions fromhardening upon exposure to air, to give compositions a moist feel to themouth, and, for particular humectants, to impart desirable sweetness offlavor to toothpaste compositions. The humectant, on a pure humectantbasis, generally comprises from about 0% to about 70% or from about 5%to about 25%, by weight of the compositions herein. Suitable humectantsfor use in compositions of the subject invention include ediblepolyhydric alcohols such as glycerin, sorbitol, xylitol, butyleneglycol, polyethylene glycol, propylene glycol and trimethyl glycine.

Flavor System

A flavor system is typically added to oral care compositions, to providea pleasant tasting composition and to effectively mask any unpleasanttaste and sensations due to certain components of the composition suchas antimicrobial actives or peroxide. Pleasant tasting compositionsimprove user compliance to prescribed or recommended use of oral careproducts. The present flavor system will comprise flavor components,such as those that have been found to be relatively stable in thepresence of usual oral care product actives, carrier materials orexcipients. The flavor system may comprise flavor ingredients includingbut not limited to peppermint oil, corn mint oil, spearmint oil, oil ofwintergreen, clove bud oil, cassia, sage, parsley oil, marjoram, lemon,lime, orange, cis-jasmone, 2,5-dimethyl-4-hydroxy-3(2H)-furanone,5-ethyl-3-hydroxy-4-methyl-2(5H)-furanone, vanillin, ethyl vanillin,2-methoxybenzaldehyde, benzaldehyde; cinnamaldehyde, hexylcinnamaldehyde, α-methyl cinnamaldehyde, ortho-methoxy cinnamaldehyde,α-amyl cinnamaldehydepropenyl guaethol, heliotropine, 4-cis-heptenal,diacetyl, methyl-ρ-tert-butyl phenyl acetate, menthol, methylsalicylate, ethyl salicylate, 1-menthyl acetate, oxanone, α-irisone,methyl cinnamate, ethyl cinnamate, butyl cinnamate, ethyl butyrate,ethyl acetate, methyl anthranilate, iso-amyl acetate, iso-amyl butyrate,allyl caproate, eugenol, eucalyptol, thymol, cinnamic alcohol, octanol,octanal, decanol, decanal, phenylethyl alcohol, benzyl alcohol,α-terpineol, linalool, limonene, citral, maltol, ethyl maltol, anethole,dihydroanethole, carvone, menthone, β-damascenone, ionone,gamma-decalactone, gamma-nonalactone, gamma-undecalactone and mixturesthereof. Generally suitable flavoring ingredients are those containingstructural features and functional groups that are less prone to redoxreactions. These include derivatives of flavor chemicals that aresaturated or contain stable aromatic rings or ester groups. Alsosuitable are flavor chemicals that may undergo some oxidation ordegradation without resulting in a significant change in the flavorcharacter or profile. The flavor ingredients may be supplied in thecomposition as single or purified chemicals or by addition of naturaloils or extracts that have preferably undergone a refining treatment toremove components that are relatively unstable and may degrade and alterthe desired flavor profile, resulting in a less acceptable product froman organoleptic standpoint. Flavoring agents are generally used in thecompositions at levels of from about 0.001% to about 5%, by weight ofthe composition.

The flavor system will typically include a sweetening agent. Suitablesweeteners include those well known in the art, including both naturaland artificial sweeteners. Some suitable water-soluble sweetenersinclude monosaccharides, disaccharides and polysaccharides such asxylose, ribose, glucose (dextrose), mannose, galactose, fructose(levulose), sucrose (sugar), maltose, invert sugar (a mixture offructose and glucose derived from sucrose), partially hydrolyzed starch,corn syrup solids, dihydrochalcones, monellin, steviosides, andglycyrrhizin. Suitable water-soluble artificial sweeteners includesoluble saccharin salts, i.e., sodium or calcium saccharin salts,cyclamate salts, the sodium, ammonium or calcium salt of3,4-dihydro-6-methyl-1,2,3-oxathiazine-4-one-2,2-dioxide, the potassiumsalt of 3,4-dihydro-6-methyl-1,2,3-oxathiazine-4-one-2,2-dioxide(acesulfame-K), the free acid form of saccharin, and the like. Othersuitable sweeteners include dipeptide based sweeteners, such asL-aspartic acid derived sweeteners, such as L-aspartyl-L-phenylalaninemethyl ester (aspartame) and materials described in U.S. Pat. No.3,492,131,L-alpha-aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-D-alaninamidehydrate, methyl esters of L-aspartyl-L-phenylglycerin andL-aspartyl-L-2,5, dihydrophenyl-glycine,L-aspartyl-2,5-dihydro-L-phenylalanine,L-aspartyl-L-(1-cyclohexylen)-alanine, and the like. Water-solublesweeteners derived from naturally occurring water-soluble sweeteners,such as a chlorinated derivative of ordinary sugar (sucrose), known, forexample, under as sucralose as well as protein based sweeteners such asthaumatoccous danielli (Thaumatin I and II) can be used. A compositiontypically contains from about 0.1% to about 10% of sweetener, by weight.

Suitable cooling agents or coolants include a wide variety of materialssuch as menthol and derivatives thereof. Among synthetic coolants, manyare derivatives of or are structurally related to menthol, i.e.,containing the cyclohexane moiety, and derivatized with functionalgroups including carboxamide, ketal, ester, ether and alcohol. Examplesinclude the ρ-menthanecarboxamide compounds such asN-ethyl-p-menthan-3-carboxamide, known commercially as “WS-3”, andothers in the series such as WS-5, WS-11, WS-14 and WS-30. An example ofa synthetic carboxamide coolant that is structurally unrelated tomenthol is N,2,3-trimethyl-2-isopropylbutanamide, known as “WS-23”.Additional suitable coolants include 3-1-menthoxypropane-1,2-diol knownas TK-10, isopulegol (under the tradename Coolact P) andρ-menthane-3,8-diol (under the tradename Coolact 38D) all available fromTakasago; menthone glycerol acetal known as MGA; menthyl esthers such asmenthyl acetate, menthyl acetoacetate, menthyl lactate known asFrescolat® supplied by Haarmann and Reimer, and monomenthyl succinateunder the tradename Physcool from V. Mane. The terms menthol and menthylas used herein include dextro- and levorotatory isomers of thesecompounds and racemic mixtures thereof. TK-10 is described in U.S. Pat.No. 4,459,425, Amano et al. WS-3 and other carboxamide cooling agentsare described for example in U.S. Pat. Nos. 4,136,163; 4,150,052;4,153,679; 4,157,384; 4,178,459 and 4,230,688. Additional N-substitutedρ-menthane carboxamides are described in WO 2005/049553A1 includingN-(4-cyanomethylphenyl)-ρ-menthanecarboxamide,N-(4-sulfamoylphenyl)-ρ-menthanecarboxamide,N-(4-cyanophenyl)-ρ-menthanecarboxamide,N-(4-acetylphenyl)-ρ-menthanecarboxamide,N-(4-hydroxymethylphenyl)-ρ-menthanecarboxamide andN-(3-hydroxy-4-methoxyphenyl)-ρ-menthanecarboxamide

In addition the flavor system may include sensates such as salivatingagents, hydration and moisturization agents, warming agents, and numbingagents. These agents are present in the compositions at a level of fromabout 0.001% to about 10% or from about 0.1% to about 1%, by weight ofthe composition. Suitable salivating agents include Jambu® manufacturedby Takasago and Optaflow® from Symrise. Examples of hydration agentsinclude polyols such as erythritol. Suitable numbing agents includebenzocaine, lidocaine, clove bud oil, and ethanol. Examples of warmingagents include ethanol, capsicum and nicotinate esters, such as benzylnicotinate.

Miscellaneous Carrier Materials

Water employed in the preparation of commercially suitable oralcompositions desirably would be of low ion content and free of organicimpurities. Water may comprise up to about 99% by weight of the aqueouscompositions herein. These amounts of water include the free water whichis added plus that which is introduced with other materials, such aswith sorbitol.

The present invention may also include an alkali metal bicarbonate salt,which may serve a number of functions including effervescent, abrasive,deodorant, buffering and adjusting pH. The present composition maycontain from about 0.5% to about 30%, from about 0.5% to about 15% orfrom about 0.5% to about 5% of an alkali metal bicarbonate such assodium bicarbonate.

The pH of the present compositions may be adjusted through the use ofbuffering agents. Buffering agents, as used herein, refer to agents thatcan be used to adjust the pH of aqueous compositions such as mouthrinses and dental solutions typically to a range of about 3 to about 8,preferably from about 3 to about 6. Buffering agents include sodiumbicarbonate, monosodium phosphate, trisodium phosphate, sodiumhydroxide, sodium carbonate, sodium acid pyrophosphate, citric acid, andsodium citrate. Buffering agents are typically included at a level offrom about 0.5% to about 10%, by weight of the present compositions.

Emulsifying agents may be employed in the present compositions. Examplesof emulsifying agents include poloxamers described above as a nonionicsurfactant, which may also function as binder, stabilizer, and otherrelated functions. Poloxamers are difunctional block-polymersterminating in primary hydroxyl groups with molecular weights rangingfrom 1,000 to above 15,000. Poloxamers are sold under the tradename ofPluronics and Pluraflo by BASF, such as Poloxamer 407 and PlurafloL4370. Other suitable emulsifying agents include the polyacrylic acidPemulen® series available from B.F. Goodrich; Vitamin E acetate; VitaminE succinate and pegylated Vitamin E.

Titanium dioxide may also be added to the present composition to addopacity to the compositions, typically at from about 0.25% to about 5%by weight of dentifrice compositions.

Other optional agents that may be used in the present compositionsinclude dimethicone copolyols selected from alkyl- andalkoxy-dimethicone copolyols, such as C12 to C20 alkyl dimethiconecopolyols and mixtures thereof. An example is cetyl dimethicone copolyolmarketed under the trade name Abil EM90. The dimethicone copolyols aidin providing positive tooth feel benefits and may be present at a levelof from about 0.01% to about 25%.

Method of Use

The present invention also relates to the use of the compositions forcontrol of staining and for controlling bacterial activity in the oralcavity which cause undesirable conditions including plaque, caries,calculus, gingivitis, and periodontal disease. The benefits of thesecompositions may increase over time when the composition is usedrepeatedly.

The method of use or treatment herein comprises contacting a subject'sdental enamel surfaces and mucosa in the mouth with the oralcompositions according to the present invention. The method may comprisebrushing with a dentifrice or rinsing with a dentifrice slurry or mouthrinse. Other methods include contacting the topical oral gel, dentureproduct, mouthspray, or other form with the subject's teeth and oralmucosa. The subject may be any person or animal in need of oral care. Byanimal is meant to include household pets or other domestic animals, oranimals kept in captivity.

For example, a method of treatment may include a person brushing a dog'steeth with one of the dentifrice compositions. Another example wouldinclude rinsing a cat's mouth with an oral composition for a sufficientamount of time to see a benefit. Pet care products such as chews andtoys may be formulated to contain the present oral compositions. Thecomposition may be incorporated into a relatively supple but strong anddurable material such as rawhide, ropes made from natural or syntheticfibers, and polymeric articles made from nylon, polyester orthermoplastic polyurethane. As the animal chews, licks or gnaws theproduct, the incorporated active elements are released into the animal'soral cavity into a salivary medium, comparable to an effective brushingor rinsing.

EXAMPLES

The following examples further describe and demonstrate embodimentswithin the scope of the present invention. These examples are givensolely for the purpose of illustration and are not to be construed aslimitations of the present invention.

Example I Mouth Rinse Compositions

Mouth rinse compositions A-F according to the present invention madeusing conventional methods are shown below with amounts of components inweight %.

Components A B C D E F Water QS QS QS QS QS QS Glycerin 5 5 5 5 7.5 10Propylene — — — 3 — — glycol Ethanol — — — — 3 10 Methyl — 0.02 0.02 — —— Paraben Propyl — 0.005 0.005 — — — Paraben CPC 0.074 0.074 0.074 0.050.07 0.1 Sucralose 0.03 0.03 0.03 0.05 0.05 0.07 Anisaldehyde 0.1 0.10.1 — — CM 0.1 0.1 0.1 — 0.05 0.1 Dextran Flavor/ 0.1 0.05 0.05 0.3 0.30.4 sensate oils Performathox 0.075 — 0.05 0.1 0.05 0.05 490

The dimensions and values disclosed herein are not to be understood asbeing strictly limited to the exact numerical values recited. Instead,unless otherwise specified, each such dimension is intended to mean boththe recited value and a functionally equivalent range surrounding thatvalue. For example, a dimension disclosed as “40 mm” is intended to mean“about 40 mm”.

All documents cited in the Detailed Description of the Invention are, inrelevant part, incorporated herein by reference; the citation of anydocument is not to be construed as an admission that it is prior artwith respect to the present invention. To the extent that any meaning ordefinition of a term in this written document conflicts with any meaningor definition of the term in a document incorporated by reference, themeaning or definition assigned to the term in this written documentshall govern.

While particular embodiments of the present invention have beenillustrated and described, it would be obvious to those skilled in theart that various other changes and modifications can be made withoutdeparting from the scope of the invention. The scope of the claimsshould not be limited by the embodiments set forth in the examples, butshould be given the broadest interpretation consistent with thedescription as a whole.

What is claimed is:
 1. A dentifrice composition, comprising: a. cationicantimicrobial agent comprising stannous fluoride; b. anionic agentcomprising sodium lauryl sulfate; c. first agent comprisingpyrophosphate, tripolyphosphate, or mixtures thereof; and d. secondagent comprising flavoring agent, the flavoring agent comprisingaldehyde, ketone, or mixtures thereof.
 2. The dentifrice composition ofclaim 1, wherein the composition comprises cocamidopropyl betaine. 3.The dentifrice composition of claim 2, wherein the composition comprisesfrom about 2% to about 30% of the first agent, by weight of thedentifrice composition.
 4. The dentifrice composition of claim 3,wherein the composition comprises from about 5% to about 25% of thefirst agent, by weight of the dentifrice composition.
 5. The dentifricecomposition of claim 2, wherein the composition is a single-phasecomposition.
 6. The dentifrice composition of claim 5, wherein theflavoring agent comprises 4-methoxybenzaldehyde (anisaldehyde);1,3-benzodioxole-5-carbaldehyde (heliotropin); 3,4-dimethoxybenzaldehyde(veratraldehyde); 3-methyl-1,2-cyclopentadione; phenethyl formate;acetophenone; phenylacetaldehyde; 4-methylacetophenone;ρ-toluacetaldehyde; 3,5,5-trimethyl-2-cyclohexene-1-one (isophorone);gamma-undecalactone; ρ-methyl cinnamaldehyde; 4-phenyl-2-butanone(benzyl acetone); octanal; 6-isopropyl-3-methyl-1-cyclohex-2-enone(piperitone); (S)-4-(1-methylethenyl)-1-cyclohexene-1-carboxaldehyde(perillaldehyde); 4-(1-methylethyl) benzaldehyde (cuminaldehyde);α-methyl cinnamaldehyde; isomenthone; menthone; carvone; decanal;3-hydroxy-2-methyl-4H-pyran-4-one (maltol); ρ-isopropylphenylacetaldehyde; trans-citral; 3-methyl-2-pentylcyclopent-2-ene-1-one(dihydrojasmone); β-napthylmethyl ketone, tiglic aldehyde, ethylvanillin, isovaleraldehyde, or mixtures thereof.
 7. The dentifricecomposition of claim 5, wherein the composition comprises saccharin. 8.The dentifrice composition of claim 7, wherein the composition comprisestitanium dioxide.
 9. The dentifrice composition of claim 8, wherein thecomposition comprises from about 0.25% to about 5% of the titaniumdioxide, by weight of the dentifrice composition.
 10. The dentifricecomposition of claim 9, wherein the flavoring agent comprises4-methoxybenzaldehyde (anisaldehyde); 1,3-benzodioxole-5-carbaldehyde(heliotropin); 3,4-dimethoxybenzaldehyde (veratraldehyde);3-methyl-1,2-cyclopentadione; phenethyl formate; acetophenone;phenylacetaldehyde; 4-methylacetophenone; ρ-toluacetaldehyde;3,5,5-trimethyl-2-cyclohexene-1-one (isophorone); gamma-undecalactone;ρ-methyl cinnamaldehyde; 4-phenyl-2-butanone (benzyl acetone); octanal;6-isopropyl-3-methyl-1-cyclohex-2-enone (piperitone);(S)-4-(1-methylethenyl)-1-cyclohexene-1-carboxaldehyde (perillaldehyde);4-(1-methylethyl) benzaldehyde (cuminaldehyde); α-methyl cinnamaldehyde;isomenthone; menthone; carvone; decanal;3-hydroxy-2-methyl-4H-pyran-4-one (maltol); ρ-isopropylphenylacetaldehyde; trans-citral; 3-methyl-2-pentylcyclopent-2-ene-1-one(dihydrojasmone); β-napthylmethyl ketone, tiglic aldehyde, ethylvanillin, isovaleraldehyde, or mixtures thereof.
 11. The dentifricecomposition of claim 10, wherein the flavoring agent comprises4-methoxybenzaldehyde (anisaldehyde); 1,3-benzodioxole-5-carbaldehyde(heliotropin); 3,4-dimethoxybenzaldehyde (veratraldehyde);3-methyl-1,2-cyclopentadione; phenethyl formate; acetophenone;phenylacetaldehyde; 4-methylacetophenone; ρ-toluacetaldehyde;3,5,5-trimethyl-2-cyclohexene-1-one (isophorone); gamma-undecalactone;ρ-methyl cinnamaldehyde, or mixtures thereof.
 12. The dentifricecomposition of claim 1, wherein the composition comprises from about0.05% to about 5% of the sodium lauryl sulfate, by weight of thedentifrice composition.
 13. The dentifrice composition of claim 12,wherein the composition comprises from about 2% to about 30% of thefirst agent, by weight of the dentifrice composition.
 14. The dentifricecomposition of claim 13, wherein the composition comprises from about 5%to about 25% of the first agent, by weight of the dentifricecomposition.
 15. The dentifrice composition of claim 14, wherein thecomposition comprises cocamidopropyl betaine.
 16. The dentifricecomposition of claim 15, wherein the composition is a single-phasecomposition.
 17. The dentifrice composition according to claim 15,wherein the compositions comprises from about 10% to about 50% of silicaabrasive, by weight of the dentifrice composition.
 18. The dentifricecomposition of claim 15, wherein the flavoring agent comprises4-methoxybenzaldehyde (anisaldehyde); 1,3-benzodioxole-5-carbaldehyde(heliotropin); 3,4-dimethoxybenzaldehyde (veratraldehyde);3-methyl-1,2-cyclopentadione; phenethyl formate; acetophenone;phenylacetaldehyde; 4-methylacetophenone; ρ-toluacetaldehyde;3,5,5-trimethyl-2-cyclohexene-1-one (isophorone); gamma-undecalactone;ρ-methyl cinnamaldehyde; 4-phenyl-2-butanone (benzyl acetone); octanal;6-isopropyl-3-methyl-1-cyclohex-2-enone (piperitone);(S)-4-(1-methylethenyl)-1-cyclohexene-1-carboxaldehyde (perillaldehyde);4-(1-methylethyl) benzaldehyde (cuminaldehyde); α-methyl cinnamaldehyde;isomenthone; menthone; carvone; decanal;3-hydroxy-2-methyl-4H-pyran-4-one (maltol); ρ-isopropylphenylacetaldehyde; trans-citral; 3-methyl-2-pentylcyclopent-2-ene-1-one(dihydrojasmone); β-napthylmethyl ketone, tiglic aldehyde, ethylvanillin, isovaleraldehyde, or mixtures thereof.
 19. The dentifricecomposition according to claim 18, wherein the flavoring agent comprises4-methoxybenzaldehyde (anisaldehyde); 1,3-benzodioxole-5-carbaldehyde(heliotropin); 3,4-dimethoxybenzaldehyde (veratraldehyde);3-methyl-1,2-cyclopentadione; phenethyl formate; acetophenone;phenylacetaldehyde; 4-methylacetophenone; ρ-toluacetaldehyde;3,5,5-trimethyl-2-cyclohexene-1-one (isophorone); gamma-undecalactone;ρ-methyl cinnamaldehyde, or mixtures thereof.
 20. The dentifricecomposition of claim 19, wherein the composition comprises zinc.